Acrp30 (also known as AdipoQ) is the murine homolog of the human Apm1 protein (this class of proteins is generically referred to as OBG3 herein). The predicted protein structure of Apm1 indicates the presence of: 1) a secreted protein signal peptide, 2) a region containing collagen repeats, and 3) a globular region (FIG. 2), which is highly conserved (FIG. 1).
Acrp30 is a circulating protein that is produced by the adipose tissue (WO 96/39429 which is hereby incorporated herein in its entirety including any figures, tables, or drawings). Acrp30 mRNA levels are significantly reduced in adipose tissue from obese ob/ob mice. Acrp30 expression is greatly increased during adipocyte differentiation and appears to be regulated by insulin. In addition, Acrp30 has been shown to reduce postprandial blood lipid levels, stimulate weight loss, and reduce plasma triglycerides in normal mice, and to promote the reduction of food intake in genetically obese mice (PCT Application No. 99/07736 which is hereby incorporated herein in its entirety including any figures, tables, or drawings).
Studies performed using just the globular region of Acrp30, termed globular Acrp30 (gAcrp30) showed that it effectively reduced body weight in mice on a high-fat cafeteria diet, as well as decreased fatty acid levels, decreased triglyceride levels, and improved glucose turnover in post-prandial tests in mice (See U.S. Provisional Application Nos. 60/176,228 and 60/198,087, both of which are hereby incorporated herein by reference including any drawings, figures, or tables).